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Honing in on Cancer Biomarkers

Research on biomarkers for cancer and other major human diseases is advancing quickly. At the recent “Oncology Biomarkers Congress,” scientists from around the world gathered to share some of their newest biomarker research.

Besides oncology biomarkers, presenters discussed companion diagnostics, patient selection, and personalized medicine. Some of the newest cancer treatments aim to individualize the therapy to the specific type of cancer and patient. The large and growing number of different genetic alterations that researchers observe in cancer cells have made it unfeasible to test for only a handful of targets. Instead, clinical testing is moving toward testing for many targets simultaneously.

“This approach of multiplexed tumor genotyping allows for the simultaneous evaluation of a broad range of common and rare tumor alterations,” said Darrell Borger, Ph.D., director of biomarker and co-director of translational research laboratories at the Massachusetts General Hospital Cancer Center. “This is important for expanding the application of targeted therapy across a greater number of patients who undergo testing, and directing those patients into the most relevant clinical trials.”

Dr. Borger and colleagues are uncovering “molecular signatures of tumors,” or collections of targets present in specific tumor types. “A molecular signature of a tumor is in essence a map of the abnormalities within a particular tumor that are thought to be critical in driving the disease process,” said Dr. Borger. “We know that each tumor will have a unique combination of genetic alterations.”

These signatures are useful because the ability to genotype a certain kind of cancer can help find the most effective treatment possible. “The more comprehensive the tumor profiling, the more detailed the roadmap we can draw for directing that patient’s care,” Dr. Borger said.

Uncovering the molecular signatures of tumors has another important role—to better understand the differences among cells within the same tumor. “Tumor heterogeneity is an important mechanism of emerging drug resistance,” said Dr. Borger. “Broad-based tumor profiling and the use of sensitive testing platforms are essential in identifying these potential mechanisms of disease resistance, so that targeted approaches can be aimed at circumventing those mechanisms.”

Target Signaling

Also working to help physicians figure out which treatments among many might work best for individual patients is Selventa. Focusing on gene expression biomarkers, Selventa researchers correlate gene expression patterns from patient data with changes in target signaling mechanisms.

“We operate on the hypothesis that patients with high or low levels of target (or downstream target) pathway signaling correspond to potential responders or nonresponders to target therapy, respectively,” said Renée Deehan Kenney, Ph.D., vp of research. “If we know who responded and who did not respond to treatment, then we can use that information to hone the biomarker using machine-learning approaches.”

Selventa is using its Systems Diagnostics (SysDx) platform to identify biomarkers used in diagnosing immune disorders such as rheumatoid arthritis (RA). Their product Clarify-RA is based on the SysDx approach using a blood biomarker. It is designed to aid clinicians in matching RA patients with those RA drugs that will be most beneficial to them. Such matching is valuable because RA is a heterogeneous disease, but different patients respond differently to the over 15 RA drugs that are available. Moreover, RA is a debilitating disease that cannot wait for a trial-and-error treatment approach.

“To compound this clinical challenge, drugs approved for RA offer about 50% improvement for only 40% of the patients,” said Dr. Deehan Kenney. For example, one biomarker Selventa found can identify RA patients who are likely to respond to anti-TNF therapy. Similarly, Selventa’s SysDx approach also found a biomarker from tumor biopsy tissue that identifies ER+ breast cancer patients whose cancer tends to progress with tamoxifen treatment.

IHC-Based Testing

Click Image To Enlarge +

Tissue samples showing adenocarcinomas from colon (top left) and pancreas (top right) after immunohistochemical staining with NPC-1C, a monoclonal antibody produced by Precision Biologics. Tissues from normal human colon (bottom left) and pancreas (bottom right) did not stain with NPC-1C in the same study.

President and CEO of Precision Biologics, Philip Arlen, M.D., discussed his company’s research on a new monoclonal antibody (NPC-1C), which targets tumors in both pancreatic and colorectal cancer. The antibody’s target is specific to tumors, and the antibody has negligible reactions with normal tissue, he said.

Precision Biologics took an unconventional tack to making NPC-1C, using a cancer vaccine that had been developed from colorectal cancer tissue removed from patients with varying stages of disease. They screened for antibodies that were specific for tumors, but nonreactive with normal tissue.

In both cell cultures and in animal models, they found that NPC-1C destroyed pancreatic cancer cells. “Furthermore, we had very encouraging Phase I/IIa data demonstrating prolongation in overall survival in patients that had exhausted all standards of therapy,” said Dr. Arlen.

Precision Biologics has developed an immunohistochemistry-based diagnostic test for expression of NPC-1C’s target. “Patients’ tumors are tested, and if the target is present, the patients can receive treatment with NPC-1C,” said Dr. Arlen. “We are also developing a diagnostic assay with NPC-1C for early detection and prognosis of colorectal and pancreatic cancer.”

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